The effects of prehospital TXA on mortality and neurologic outcomes in patients with traumatic intracranial hemorrhage: a subgroup analysis from the prehospital TXA for TBI trial.

BACKGROUND: In the Prehospital Tranexamic Acid (TXA) for TBI Trial, TXA administered within two hours of injury in the out-of-hospital setting did not reduce mortality in all patients with moderate/severe traumatic brain injury (TBI). We examined the association between TXA dosing arms, neurologic outcome, and mortality in patients with intracranial hemorrhage (ICH) on computed tomography (CT). METHODS: This was a secondary analysis of the Prehospital Tranexamic Acid for TBI Trial (ClinicalTrials.gov [NCT01990768]) that randomized adults with moderate/severe TBI (Glasgow Coma Scale<13) and systolic blood pressure > =90 mmHg within two hours of injury to a 2-gram out-of-hospital TXA bolus followed by an in-hospital saline infusion, a 1-gram out-of-hospital TXA bolus/1-gram in-hospital TXA infusion, or an out-of-hospital saline bolus/in-hospital saline infusion (placebo). This analysis included the subgroup with ICH on initial CT. Primary outcomes included 28-day mortality, 6-month Glasgow Outcome Scale-Extended (GOSE) < = 4, and 6-month Disability Rating Scale (DRS). Outcomes were modeled using linear regression with robust standard errors. RESULTS: The primary trial included 966 patients. Among 541 participants with ICH, 28-day mortality was lower in the 2-gram TXA bolus group (17%) compared to the other two groups (1-gram bolus/1-gram infusion 26%, placebo 27%). The estimated adjusted difference between the 2-gram bolus and placebo groups was -8·5 percentage points (95% CI, -15.9 to -1.0) and between the 2-gram bolus and 1-gram bolus/1-gram infusion groups was -10.2 percentage points (95% CI, -17.6 to -2.9). DRS at 6 months was lower in the 2-gram TXA bolus group than the 1-gram bolus/1-gram infusion (estimated difference -2.1 [95% CI, -4.2 to -0.02]) and placebo groups (-2.2 [95% CI, -4.3, -0.2]). Six-month GOSE did not differ among groups. CONCLUSIONS: A 2-gram out-of-hospital TXA bolus in patients with moderate/severe TBI and ICH resulted in lower 28-day mortality and lower 6-month DRS than placebo and standard TXA dosing. LEVEL OF EVIDENCE: Therapeutic/Care Management, Level II.

Adverse Safety Events in Emergency Medical Services Care of Children With Out-of-Hospital Cardiac Arrest.

Importance: Survival for children with out-of-hospital cardiac arrest (OHCA) remains poor despite improvements in adult OHCA survival. Objective: To characterize the frequency of and factors associated with adverse safety events (ASEs) in pediatric OHCA. Design, Setting, and Participants: This population-based retrospective cohort study examined patient care reports from 51 emergency medical services (EMS) agencies in California, Georgia, Oregon, Pennsylvania, Texas, and Wisconsin for children younger than 18 years with an OHCA in which resuscitation was attempted by EMS personnel between 2013 and 2019. Medical record review was conducted from January 2019 to April 2022 and data analysis from October 2022 to February 2023. Main Outcomes and Measure: Severe ASEs during the patient encounter (eg, failure to give an indicated medication, 10-fold medication overdose). Results: A total of 1019 encounters of EMS-treated pediatric OHCA were evaluated; 465 patients (46%) were younger than 12 months. At least 1 severe ASE occurred in 610 patients (60%), and 310 patients (30%) had 2 or more. Neonates had the highest frequency of ASEs. The most common severe ASEs involved epinephrine administration (332 [30%]), vascular access (212 [19%]), and ventilation (160 [14%]). In multivariable logistic regression, the only factor associated with severe ASEs was young age. Neonates with birth-related and non-birth-related OHCA had greater odds of a severe ASE compared with adolescents (birth-related: odds ratio [OR], 7.0; 95% CI, 3.1-16.1; non-birth-related: OR, 3.4; 95% CI, 1.2-9.6). Conclusions and Relevance: In this large geographically diverse cohort of children with EMS-treated OHCA, 60% of all patients experienced at least 1 severe ASE. The odds of a severe ASE were higher for neonates than adolescents and even higher when the cardiac arrest was birth related. Given the national increase in out-of-hospital births and ongoing poor outcomes of OHCA in young children, these findings represent an urgent call to action to improve care delivery and training for this population.

Bag-Valve-Mask Ventilation and Survival From Out-of-Hospital Cardiac Arrest: A Multicenter Study.

BACKGROUND: Few studies have measured ventilation during early cardiopulmonary resuscitation (CPR) before advanced airway placement. Resuscitation guidelines recommend pauses after every 30 chest compressions to deliver ventilations. The effectiveness of bag-valve-mask ventilation delivered during the pause in chest compressions is unknown. We sought to determine: (1) the incidence of lung inflation with bag-valve-mask ventilation during 30:2 CPR; and (2) the association of ventilation with outcomes after out-of-hospital cardiac arrest. METHODS: We studied patients with out-of-hospital cardiac arrest from 6 sites of the Resuscitation Outcomes Consortium CCC study (Trial of Continuous Compressions versus Standard CPR in Patients with Out-of-Hospital Cardiac Arrest). We analyzed patients assigned to the 30:2 CPR arm with ≥2 minutes of thoracic bioimpedance signal recorded with a cardiac defibrillator/monitor. Detectable ventilation waveforms were defined as having a bioimpedance amplitude ≥0.5 Ω (corresponding to ≥250 mL VT) and a duration ≥1 s. We defined a chest compression pause as a 3- to 15-s break in chest compressions. We compared the incidence of ventilation and outcomes in 2 groups: patients with ventilation waveforms in <50% of pauses (group 1) versus those with waveforms in ≥50% of pauses (group 2). RESULTS: Among 1976 patients, the mean age was 65 years; 66% were male. From the start of chest compressions until advanced airway placement, mean±SD duration of 30:2 CPR was 9.8±4.9 minutes. During this period, we identified 26 861 pauses in chest compressions; 60% of patients had ventilation waveforms in <50% of pauses (group 1, n=1177), and 40% had waveforms in ≥50% of pauses (group 2, n=799). Group 1 had a median of 12 pauses and 2 ventilations per patient versus group 2, which had 12 pauses and 12 ventilations per patient. Group 2 had higher rates of prehospital return of spontaneous circulation (40.7% versus 25.2%; P<0.0001), survival to hospital discharge (13.5% versus 4.1%; P<0.0001), and survival with favorable neurological outcome (10.6% versus 2.4%; P<0.0001). These associations persisted after adjustment for confounders. CONCLUSIONS: In this study, lung inflation occurred infrequently with bag-valve-mask ventilation during 30:2 CPR. Lung inflation in ≥50% of pauses was associated with improved return of spontaneous circulation, survival, and survival with favorable neurological outcome.

Prevalence of Symptoms ≤12 Months After Acute Illness, by COVID-19 Testing Status Among Adults - United States, December 2020-March 2023.

To further the understanding of post-COVID conditions, and provide a more nuanced description of symptom progression, resolution, emergence, and reemergence after SARS-CoV-2 infection or COVID-like illness, analysts examined data from the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE), a prospective multicenter cohort study. This report includes analysis of data on self-reported symptoms collected from 1,296 adults with COVID-like illness who were tested for SARS-CoV-2 using a Food and Drug Administration-approved polymerase chain reaction or antigen test at the time of enrollment and reported symptoms at 3-month intervals for 12 months. Prevalence of any symptom decreased substantially between baseline and the 3-month follow-up, from 98.4% to 48.2% for persons who received a positive SARS-CoV-2 test results (COVID test-positive participants) and from 88.2% to 36.6% for persons who received negative SARS-CoV-2 test results (COVID test-negative participants). Persistent symptoms decreased through 12 months; no difference between the groups was observed at 12 months (prevalence among COVID test-positive and COVID test-negative participants = 18.3% and 16.1%, respectively; p>0.05). Both groups reported symptoms that emerged or reemerged at 6, 9, and 12 months. Thus, these symptoms are not unique to COVID-19 or to post-COVID conditions. Awareness that symptoms might persist for up to 12 months, and that many symptoms might emerge or reemerge in the year after COVID-like illness, can assist health care providers in understanding the clinical signs and symptoms associated with post-COVID-like conditions.

Association Between SARS-CoV-2 Variants and Frequency of Acute Symptoms: Analysis of a Multi-institutional Prospective Cohort Study-December 20, 2020-June 20, 2022.

Background: While prior work examining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern focused on hospitalization and death, less is known about differences in clinical presentation. We compared the prevalence of acute symptoms across pre-Delta, Delta, and Omicron. Methods: We conducted an analysis of the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE), a cohort study enrolling symptomatic SARS-CoV-2-positive participants. We determined the association between the pre-Delta, Delta, and Omicron time periods and the prevalence of 21 coronavirus disease 2019 (COVID-19) acute symptoms. Results: We enrolled 4113 participants from December 2020 to June 2022. Pre-Delta vs Delta vs Omicron participants had increasing sore throat (40.9%, 54.6%, 70.6%; P < .001), cough (50.9%, 63.3%, 66.7%; P < .001), and runny noses (48.9%, 71.3%, 72.9%; P < .001). We observed reductions during Omicron in chest pain (31.1%, 24.2%, 20.9%; P < .001), shortness of breath (42.7%, 29.5%, 27.5%; P < .001), loss of taste (47.1%, 61.8%, 19.2%; P < .001), and loss of smell (47.5%, 55.6%, 20.0%; P < .001). After adjustment, those infected during Omicron had significantly higher odds of sore throat vs pre-Delta (odds ratio [OR], 2.76; 95% CI, 2.26-3.35) and Delta (OR, 1.96; 95% CI, 1.69-2.28). Conclusions: Participants infected during Omicron were more likely to report symptoms of common respiratory viruses, such as sore throat, and less likely to report loss of smell and taste. Trial registration: NCT04610515.

Long COVID Clinical Phenotypes up to 6 Months After Infection Identified by Latent Class Analysis of Self-Reported Symptoms.

Background: The prevalence, incidence, and interrelationships of persistent symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection vary. There are limited data on specific phenotypes of persistent symptoms. Using latent class analysis (LCA) modeling, we sought to identify whether specific phenotypes of COVID-19 were present 3 months and 6 months post-infection. Methods: This was a multicenter study of symptomatic adults tested for SARS-CoV-2 with prospectively collected data on general symptoms and fatigue-related symptoms up to 6 months postdiagnosis. Using LCA, we identified symptomatically homogenous groups among COVID-positive and COVID-negative participants at each time period for both general and fatigue-related symptoms. Results: Among 5963 baseline participants (4504 COVID-positive and 1459 COVID-negative), 4056 had 3-month and 2856 had 6-month data at the time of analysis. We identified 4 distinct phenotypes of post-COVID conditions (PCCs) at 3 and 6 months for both general and fatigue-related symptoms; minimal-symptom groups represented 70% of participants at 3 and 6 months. When compared with the COVID-negative cohort, COVID-positive participants had higher occurrence of loss of taste/smell and cognition problems. There was substantial class-switching over time; those in 1 symptom class at 3 months were equally likely to remain or enter a new phenotype at 6 months. Conclusions: We identified distinct classes of PCC phenotypes for general and fatigue-related symptoms. Most participants had minimal or no symptoms at 3 and 6 months of follow-up. Significant proportions of participants changed symptom groups over time, suggesting that symptoms present during the acute illness may differ from prolonged symptoms and that PCCs may have a more dynamic nature than previously recognized. Clinical Trials Registration. NCT04610515.

Impedance-Based Ventilation Detection and Signal Quality Control During Out-of-Hospital Cardiopulmonary Resuscitation.

Feedback on ventilation could help improve cardiopulmonary resuscitation quality and survival from out-of-hospital cardiac arrest (OHCA). However, current technology that monitors ventilation during OHCA is very limited. Thoracic impedance (TI) is sensitive to air volume changes in the lungs, allowing ventilations to be identified, but is affected by artifacts due to chest compressions and electrode motion. This study introduces a novel algorithm to identify ventilations in TI during continuous chest compressions in OHCA. Data from 367 OHCA patients were included, and 2551 one-minute TI segments were extracted. Concurrent capnography data were used to annotate 20724 ground truth ventilations for training and evaluation. A three-step procedure was applied to each TI segment: First, bidirectional static and adaptive filters were applied to remove compression artifacts. Then, fluctuations potentially due to ventilations were located and characterized. Finally, a recurrent neural network was used to discriminate ventilations from other spurious fluctuations. A quality control stage was also developed to anticipate segments where ventilation detection could be compromised. The algorithm was trained and tested using 5-fold cross-validation, and outperformed previous solutions in the literature on the study dataset. The median (interquartile range, IQR) per-segment and per-patient F 1-scores were 89.1 (70.8-99.6) and 84.1 (69.0-93.9), respectively. The quality control stage identified most low performance segments. For the 50% of segments with highest quality scores, the median per-segment and per-patient F 1-scores were 100.0 (90.9-100.0) and 94.3 (86.5-97.8). The proposed algorithm could allow reliable, quality-conditioned feedback on ventilation in the challenging scenario of continuous manual CPR in OHCA.

Temporal analysis of continuous chest compression rate and depth performed by firefighters during out of hospital cardiac arrest.

BACKGROUND: Quality of chest compressions (CC) during cardiopulmonary resuscitation (CPR) often do not meet guideline recommendations for rate and depth. This may be due to the fatiguing nature of physically compressing a patient's chest, meaning that CPR quality reduces over time. OBJECTIVE: This analysis investigates the effect of CPR duration on the performance of continuous CCs delivered by firefighters equipped with CPR feedback devices. METHODS: Data were collected from a first responder group which used CPR feedback and automatic external defibrillator devices when attending out-of-hospital cardiac arrest events. Depth and rate of CC were analysed for 134 patients. Mean CC depth and rate were calculated every 5 s during two-minute episodes of CPR. Regression models were created to evaluate the relationship between applied CC depth and rate as a function of time. RESULTS: Mean (SD) CC depth during the investigation was 48 (9) mm. An inverse relationship was observed between CC depth and CPR duration, where CC depth decreased by 3.39 mm, over two-minutes of CPR (p < 0.001). Mean (SD) CC rate was 112.06 (5.87) compressions per minute. No significant relationship was observed between CC rate and CPR duration (p = 0.077). Mean depth was within guideline range for 33.58% of patient events, while guideline rate was observed in 92.54% of cases. CONCLUSIONS: A reduction in CC depth was observed during two-minutes of continuous CCs while CC rate was not affected. One third of patients received a mean CC depth within guideline range (50 to 60 mm).

Severe Fatigue and Persistent Symptoms at 3 Months Following Severe Acute Respiratory Syndrome Coronavirus 2 Infections During the Pre-Delta, Delta, and Omicron Time Periods: A Multicenter Prospective Cohort Study.

BACKGROUND: Most research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants focuses on initial symptomatology with limited longer-term data. We characterized prevalences of prolonged symptoms 3 months post-SARS-CoV-2 infection across 3 variant time-periods (pre-Delta, Delta, and Omicron). METHODS: This multicenter prospective cohort study of adults with acute illness tested for SARS-CoV-2 compared fatigue severity, fatigue symptoms, organ system-based symptoms, and ≥3 symptoms across variants among participants with a positive ("COVID-positive") or negative SARS-CoV-2 test ("COVID-negative") at 3 months after SARS-CoV-2 testing. Variant periods were defined by dates with ≥50% dominant strain. We performed multivariable logistic regression modeling to estimate independent effects of variants adjusting for sociodemographics, baseline health, and vaccine status. RESULTS: The study included 2402 COVID-positive and 821 COVID-negative participants. Among COVID-positives, 463 (19.3%) were pre-Delta, 1198 (49.9%) Delta, and 741 (30.8%) Omicron. The pre-Delta COVID-positive cohort exhibited more prolonged severe fatigue (16.7% vs 11.5% vs 12.3%; P = .017) and presence of ≥3 prolonged symptoms (28.4% vs 21.7% vs 16.0%; P < .001) compared with the Delta and Omicron cohorts. No differences were seen in the COVID-negatives across time-periods. In multivariable models adjusted for vaccination, severe fatigue and odds of having ≥3 symptoms were no longer significant across variants. CONCLUSIONS: Prolonged symptoms following SARS-CoV-2 infection were more common among participants infected during pre-Delta than with Delta and Omicron; however, these differences were no longer significant after adjusting for vaccination status, suggesting a beneficial effect of vaccination on risk of long-term symptoms. Clinical Trials Registration. NCT04610515.

Three-Month Symptom Profiles Among Symptomatic Adults With Positive and Negative Severe Acute Respiratory Syndrome Coronavirus 2 Tests: A Prospective Cohort Study From the INSPIRE Group.

BACKGROUND: Long-term symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are a major concern, yet their prevalence is poorly understood. METHODS: We conducted a prospective cohort study comparing adults with SARS-CoV-2 infection (coronavirus disease-positive [COVID+]) with adults who tested negative (COVID-), enrolled within 28 days of a Food and Drug Administration (FDA)-approved SARS-CoV-2 test result for active symptoms. Sociodemographic characteristics, symptoms of SARS-CoV-2 infection (assessed with the Centers for Disease Control and Prevention [CDC] Person Under Investigation Symptom List), and symptoms of post-infectious syndromes (ie, fatigue, sleep quality, muscle/joint pains, unrefreshing sleep, and dizziness/fainting, assessed with CDC Short Symptom Screener for myalgic encephalomyelitis/chronic fatigue syndrome) were assessed at baseline and 3 months via electronic surveys sent via text or email. RESULTS: Among the first 1000 participants, 722 were COVID+ and 278 were COVID-. Mean age was 41.5 (SD 15.2); 66.3% were female, 13.4% were Black, and 15.3% were Hispanic. At baseline, SARS-CoV-2 symptoms were more common in the COVID+ group than the COVID- group. At 3 months, SARS-CoV-2 symptoms declined in both groups, although were more prevalent in the COVID+ group: upper respiratory symptoms/head/eyes/ears/nose/throat (HEENT; 37.3% vs 20.9%), constitutional (28.8% vs 19.4%), musculoskeletal (19.5% vs 14.7%), pulmonary (17.6% vs 12.2%), cardiovascular (10.0% vs 7.2%), and gastrointestinal (8.7% vs 8.3%); only 50.2% and 73.3% reported no symptoms at all. Symptoms of post-infectious syndromes were similarly prevalent among the COVID+ and COVID- groups at 3 months. CONCLUSIONS: Approximately half of COVID+ participants, as compared with one-quarter of COVID- participants, had at least 1 SARS-CoV-2 symptom at 3 months, highlighting the need for future work to distinguish long COVID. CLINICAL TRIALS REGISTRATION: NCT04610515.

Methods for calculating ventilation rates during resuscitation from out-of-hospital cardiac arrest.

OBJECTIVE: Ventilation control is important during resuscitation from out-of-hospital cardiac arrest (OHCA). We compared different methods for calculating ventilation rates (VR) during OHCA. METHODS: We analyzed data from the Pragmatic Airway Resuscitation Trial, identifying ventilations through capnogram recordings. We determined VR by: 1) counting the number of breaths within a time epoch ("counted" VR), and 2) calculating the mean of the inverse of measured time between breaths within a time epoch ("measured" VR). We repeated the VR estimates using different time epochs (10, 20, 30, 60 sec). We defined hypo- and hyperventilation as VR <6 and >12 breaths/min, respectively. We assessed differences in estimated hypo- and hyperventilation with each VR measurement technique. RESULTS: Of 3,004 patients, data were available for 1,010. With the counted method, total hypoventilation increased with longer time epochs ([10-s epoch: 75 sec hypoventilation] to [60-s epoch: 97 sec hypoventilation]). However, with the measured method, total hypoventilation decreased with longer time epochs ([10-s epoch: 223 sec hypoventilation] to [60-s epoch: 150 sec hypoventilation]). With the counted method, the total duration of hyperventilation decreased with longer time epochs ([10-s epochs: 35 sec hyperventilation] to [60-s epoch: 0 sec hyperventilation]). With the measured method, total hyperventilation decreased with longer time epochs ([10-s epoch: 78 sec hyperventilation] to [60-s epoch: 0 sec hyperventilation]). Differences between the measured and counted estimates were smallest with a 60-s time epoch. CONCLUSIONS: Quantifications of hypo- and hyperventilation vary with the applied measurement methods. Measurement methods are important when characterizing ventilation rates in OHCA.

Ethnic and racial differences in self-reported symptoms, health status, activity level, and missed work at 3 and 6 months following SARS-CoV-2 infection.

Introduction: Data on ethnic and racial differences in symptoms and health-related impacts following SARS-CoV-2 infection are limited. We aimed to estimate the ethnic and racial differences in symptoms and health-related impacts 3 and 6 months after the first SARS-CoV-2 infection. Methods: Participants included adults with SARS-CoV-2 infection enrolled in a prospective multicenter US study between 12/11/2020 and 7/4/2022 as the primary cohort of interest, as well as a SARS-CoV-2-negative cohort to account for non-SARS-CoV-2-infection impacts, who completed enrollment and 3-month surveys (N = 3,161; 2,402 SARS-CoV-2-positive, 759 SARS-CoV-2-negative). Marginal odds ratios were estimated using GEE logistic regression for individual symptoms, health status, activity level, and missed work 3 and 6 months after COVID-19 illness, comparing each ethnicity or race to the referent group (non-Hispanic or white), adjusting for demographic factors, social determinants of health, substance use, pre-existing health conditions, SARS-CoV-2 infection status, COVID-19 vaccination status, and survey time point, with interactions between ethnicity or race and time point, ethnicity or race and SARS-CoV-2 infection status, and SARS-CoV-2 infection status and time point. Results: Following SARS-CoV-2 infection, the majority of symptoms were similar over time between ethnic and racial groups. At 3 months, Hispanic participants were more likely than non-Hispanic participants to report fair/poor health (OR: 1.94; 95%CI: 1.36-2.78) and reduced activity (somewhat less, OR: 1.47; 95%CI: 1.06-2.02; much less, OR: 2.23; 95%CI: 1.38-3.61). At 6 months, differences by ethnicity were not present. At 3 months, Other/Multiple race participants were more likely than white participants to report fair/poor health (OR: 1.90; 95% CI: 1.25-2.88), reduced activity (somewhat less, OR: 1.72; 95%CI: 1.21-2.46; much less, OR: 2.08; 95%CI: 1.18-3.65). At 6 months, Asian participants were more likely than white participants to report fair/poor health (OR: 1.88; 95%CI: 1.13-3.12); Black participants reported more missed work (OR, 2.83; 95%CI: 1.60-5.00); and Other/Multiple race participants reported more fair/poor health (OR: 1.83; 95%CI: 1.10-3.05), reduced activity (somewhat less, OR: 1.60; 95%CI: 1.02-2.51; much less, OR: 2.49; 95%CI: 1.40-4.44), and more missed work (OR: 2.25; 95%CI: 1.27-3.98). Discussion: Awareness of ethnic and racial differences in outcomes following SARS-CoV-2 infection may inform clinical and public health efforts to advance health equity in long-term outcomes.

Association of Initial SARS-CoV-2 Test Positivity With Patient-Reported Well-being 3 Months After a Symptomatic Illness.

Importance: Long-term sequelae after symptomatic SARS-CoV-2 infection may impact well-being, yet existing data primarily focus on discrete symptoms and/or health care use. Objective: To compare patient-reported outcomes of physical, mental, and social well-being among adults with symptomatic illness who received a positive vs negative test result for SARS-CoV-2 infection. Design, Setting, and Participants: This cohort study was a planned interim analysis of an ongoing multicenter prospective longitudinal registry study (the Innovative Support for Patients With SARS-CoV-2 Infections Registry [INSPIRE]). Participants were enrolled from December 11, 2020, to September 10, 2021, and comprised adults (aged ≥18 years) with acute symptoms suggestive of SARS-CoV-2 infection at the time of receipt of a SARS-CoV-2 test approved by the US Food and Drug Administration. The analysis included the first 1000 participants who completed baseline and 3-month follow-up surveys consisting of questions from the 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29; 7 subscales, including physical function, anxiety, depression, fatigue, social participation, sleep disturbance, and pain interference) and the PROMIS Short Form-Cognitive Function 8a scale, for which population-normed T scores were reported. Exposures: SARS-CoV-2 status (positive or negative test result) at enrollment. Main Outcomes and Measures: Mean PROMIS scores for participants with positive COVID-19 tests vs negative COVID-19 tests were compared descriptively and using multivariable regression analysis. Results: Among 1000 participants, 722 (72.2%) received a positive COVID-19 result and 278 (27.8%) received a negative result; 406 of 998 participants (40.7%) were aged 18 to 34 years, 644 of 972 (66.3%) were female, 833 of 984 (84.7%) were non-Hispanic, and 685 of 974 (70.3%) were White. A total of 282 of 712 participants (39.6%) in the COVID-19-positive group and 147 of 275 participants (53.5%) in the COVID-19-negative group reported persistently poor physical, mental, or social well-being at 3-month follow-up. After adjustment, improvements in well-being were statistically and clinically greater for participants in the COVID-19-positive group vs the COVID-19-negative group only for social participation (ß = 3.32; 95% CI, 1.84-4.80; P < .001); changes in other well-being domains were not clinically different between groups. Improvements in well-being in the COVID-19-positive group were concentrated among participants aged 18 to 34 years (eg, social participation: ß = 3.90; 95% CI, 1.75-6.05; P < .001) and those who presented for COVID-19 testing in an ambulatory setting (eg, social participation: ß = 4.16; 95% CI, 2.12-6.20; P < .001). Conclusions and Relevance: In this study, participants in both the COVID-19-positive and COVID-19-negative groups reported persistently poor physical, mental, or social well-being at 3-month follow-up. Although some individuals had clinically meaningful improvements over time, many reported moderate to severe impairments in well-being 3 months later. These results highlight the importance of including a control group of participants with negative COVID-19 results for comparison when examining the sequelae of COVID-19.

Variation in coronary angiography use in Out-of-Hospital cardiac arrest.

INTRODUCTION: Multiple studies have examined the association of early coronary angiography (CAG) among out-of-hospital cardiac arrest (OHCA) patients with conflicting results. However, patterns of use of CAG among OHCA patients in real-world settings are not well-described. METHODS: Utilizing data from the Resuscitation Outcomes Consortium's Continuous Chest Compressions trial for our analysis, we stratified patients based on initial arrest rhythm and ST-elevation on initial post-resuscitation electrocardiogram (ECG) and examined the rates of CAG in resuscitated patients. We also examined the rates of CAG across different trial clusters in the overall study population as well as in pre-specified patient subgroups RESULTS: Of 26,148 patients in the CCC trial, 5,608 survived to hospital admission and were enrolled in the study. Among them, 26 % underwent CAG. Patients with ST-elevation underwent CAG at a significantly higher rate than patients presenting without ST-elevation (70 % vs 31 %, p < 0.001). Similarly, patients presenting with shockable rhythms underwent CAG more frequently compared with patients with non-shockable rhythms (28 % vs 5 %, p < 0.001). There was marked variation in CAG frequency across different trial clusters with the proportion of patients within a trial cluster receiving CAG ranging from 4 % - 41 %. The proportion varied more among patients with ST-elevation (16 % - 82 %) or initial shockable rhythm (11 % - 75 %) compared with no ST-elevation (2 % - 28 %) or initial non-shockable rhythm (0 % - 19 %). CONCLUSION: Among a national cohort of OHCA patients, large variation in the use of CAG exists, highlighting the existing uncertainty regarding perceived benefit from early CAG in OHCA.

Assessment of intensive care unit-free and ventilator-free days as alternative outcomes in the pragmatic airway resuscitation trial.

OBJECTIVE: We sought to evaluate the utility and validity of ICU-free days and ventilator-free days as candidate outcomes for OHCA trials. METHODS: We conducted a secondary analysis of the Pragmatic Airway Resuscitation Trial. We determined ICU-free (days alive and out of ICU during the first 30 days) and ventilator-free days (days alive and without mechanical ventilation). We determined ICU-free and ventilator-free day distributions and correlations with Modified Rankin Scale (MRS). We tested associations with trial interventions (laryngeal tube (LT), endotracheal intubation (ETI)) using continuous (t-test), non-parametric (Wilcoxon Rank-Sum test - WRS), count (negative binomial - NB) and survival models (Cox proportional hazards (CPH) and competing risks regression (CRR)). We conducted bootstrapped simulations to estimate statistical power. MAIN RESULTS: ICU-free days was skewed; median 0 days (IQR 0, 0), survivors only 24 (18, 27). Ventilator-free days was skewed; median 0 (IQR 0, 0) days, survivors only 27 (IQR 23, 28). ICU-free and ventilator-free days correlated with MRS (Spearman's ρ = -0.95 and -0.97). LT was associated with higher ICU-free days using t-test (p = 0.001), WRS (p = 0.003), CPH (p = 0.02) and CRR (p = 0.04), but not NB (p = 0.13). LT was associated with higher ventilator-free days using t-test (p = 0.001), WRS (p = 0.001) and CRR (p = 0.03), but not NB (p = 0.13) or CPH (p = 0.13). Simulations suggested that t-test and WRS would have had the greatest power to detect the observed ICU- and ventilator-free days differences. CONCLUSION: ICU-free and ventilator-free days correlated with MRS and differentiated trial interventions. ICU-free and ventilator-free days may have utility in the design of OHCA trials.

Improving Emergency Medical Services Information Exchange: Methods for Automating Entity Resolution.

The 21st century has seen an enormous growth in emergency medical services (EMS) information technology systems, with corresponding accumulation of large volumes of data. Despite this growth, integration efforts between EMS-based systems and electronic health records, and public-sector databases have been limited due to inconsistent data structure, data missingness, and policy and regulatory obstacles. Efforts to integrate EMS systems have benefited from the evolving science of entity resolution and record linkage. In this chapter, we present the history and fundamentals of record linkage techniques, an overview of past uses of this technology in EMS, and a look into the future of record linkage techniques for integrating EMS data systems including the use of machine learning-based techniques.

Airway strategy and ventilation rates in the pragmatic airway resuscitation trial.

BACKGROUND: We sought to describe ventilation rates during out-of-hospital cardiac arrest (OHCA) resuscitation and their associations with airway management strategy and outcomes. METHODS: We analyzed continuous end-tidal carbon dioxide capnography data from adult OHCA enrolled in the Pragmatic Airway Resuscitation Trial (PART). Using automated signal processing techniques, we determined continuous ventilation rates for consecutive 10-second epochs after airway insertion. We defined hypoventilation as a ventilation rate < 6 breaths/min. We defined hyperventilation as a ventilation rate > 12 breaths/min. We compared differences in total and percentage post-airway hyper- and hypoventilation between airway interventions (laryngeal tube (LT) vs. endotracheal intubation (ETI)). We also determined associations between hypo-/hyperventilation and OHCA outcomes (ROSC, 72-hour survival, hospital survival, hospital survival with favorable neurologic status). RESULTS: Adequate post-airway capnography were available for 1,010 (LT n = 714, ETI n = 296) of 3,004 patients. Median ventilation rates were: LT 8.0 (IQR 6.5-9.6) breaths/min, ETI 7.9 (6.5-9.7) breaths/min. Total duration and percentage of post-airway time with hypoventilation were similar between LT and ETI: median 1.8 vs. 1.7 minutes, p = 0.94; median 10.5% vs. 11.5%, p = 0.60. Total duration and percentage of post-airway time with hyperventilation were similar between LT and ETI: median 0.4 vs. 0.4 minutes, p = 0.91; median 2.1% vs. 1.9%, p = 0.99. Hypo- and hyperventilation exhibited limited associations with OHCA outcomes. CONCLUSION: In the PART Trial, EMS personnel delivered post-airway ventilations at rates satisfying international guidelines, with only limited hypo- or hyperventilation. Hypo- and hyperventilation durations did not differ between airway management strategy and exhibited uncertain associations with OCHA outcomes.

Procainamide for shockable rhythm cardiac arrest in the Resuscitation Outcome Consortium.

BACKGROUND: With recent negative studies of amiodarone and lidocaine for cardiac arrest, research into other antiarrhythmics is warranted. Literature on procainamide in cardiac arrest is limited. We evaluated procainamide for out-of-hospital cardiac arrests (OHCA) from the Resuscitation Outcomes Consortium (ROC). METHODS: We included all ROC Epistry 3 OHCAs with an initial shockable rhythm that received an antiarrhythmic. We stratified cases by antiarrhythmic: procainamide, amiodarone, or lidocaine. The outcomes were prehospital return of spontaneous circulation (ROSC), ROSC in the ED, and survival to hospital discharge. We defined propensity scores based on possible confounders utilizing 1:1 propensity score matching to compare procainamide to amiodarone and lidocaine. We analyzed the matched data using logistic regression. We also used multivariable logistic regression to evaluate the association between antiarrhythmic and outcomes. RESULTS: 3087 subjects met inclusion criteria; 51 patients received only procainamide, 1776 received amiodarone, and 1418 received lidocaine. On propensity score analysis and compared to procainamide, amiodarone had similar prehospital ROSC (OR 0.7, 95% CI 0.3-1.8), ED ROSC (OR 0.6, 95% CI 0.3-1.3), and survival (OR 1.0, 95% CI 0.3-3.1). Lidocaine also had a similar prehospital ROSC (OR 0.9, 95% CI 0.4-2.2), ED ROSC (OR 1.2, 95% CI 0.5-2.7), and survival (OR 1.4, 95% CI 0.5-4.0). However, using multivariable regression, amiodarone had lower prehospital ROSC than procainamide (aOR 0.3, 95% CI 0.1-0.6). CONCLUSIONS: While associated with increased prehospital ROSC when compared with amiodarone using multivariable regression, procainamide otherwise had similar prehospital ROSC, ED ROSC, and survival. The role of procainamide in OHCA remains unclear.

Study protocol for the Innovative Support for Patients with SARS-COV-2 Infections Registry (INSPIRE): A longitudinal study of the medium and long-term sequelae of SARS-CoV-2 infection.

BACKGROUND: Reports on medium and long-term sequelae of SARS-CoV-2 infections largely lack quantification of incidence and relative risk. We describe the rationale and methods of the Innovative Support for Patients with SARS-CoV-2 Registry (INSPIRE) that combines patient-reported outcomes with data from digital health records to understand predictors and impacts of SARS-CoV-2 infection. METHODS: INSPIRE is a prospective, multicenter, longitudinal study of individuals with symptoms of SARS-CoV-2 infection in eight regions across the US. Adults are eligible for enrollment if they are fluent in English or Spanish, reported symptoms suggestive of acute SARS-CoV-2 infection, and if they are within 42 days of having a SARS-CoV-2 viral test (i.e., nucleic acid amplification test or antigen test), regardless of test results. Recruitment occurs in-person, by phone or email, and through online advertisement. A secure online platform is used to facilitate the collation of consent-related materials, digital health records, and responses to self-administered surveys. Participants are followed for up to 18 months, with patient-reported outcomes collected every three months via survey and linked to concurrent digital health data; follow-up includes no in-person involvement. Our planned enrollment is 4,800 participants, including 2,400 SARS-CoV-2 positive and 2,400 SARS-CoV-2 negative participants (as a concurrent comparison group). These data will allow assessment of longitudinal outcomes from SARS-CoV-2 infection and comparison of the relative risk of outcomes in individuals with and without infection. Patient-reported outcomes include self-reported health function and status, as well as clinical outcomes including health system encounters and new diagnoses. RESULTS: Participating sites obtained institutional review board approval. Enrollment and follow-up are ongoing. CONCLUSIONS: This study will characterize medium and long-term sequelae of SARS-CoV-2 infection among a diverse population, predictors of sequelae, and their relative risk compared to persons with similar symptomatology but without SARS-CoV-2 infection. These data may inform clinical interventions for individuals with sequelae of SARS-CoV-2 infection.